A systems toxicology approach to the surface functionality control of graphene-cell interactions
A systems toxicology approach to the surface functionality control of graphene-cell interactions
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DOI：
10.1016/j.biomaterials.2013.09.108
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发表时间：
2014-01-01
期刊：
影响因子：
14
通讯作者：
Choi, Jinhee
中科院分区：
文献类型：
--
作者：
Chatterjee, Nivedita;Eom, Hyun-Jeong;Choi, Jinhee
人们对石墨烯纳米材料及其衍生物可能对环境健康和安全造成的影响表示了相当大的担忧，这源于其潜在的广泛应用。我们通过在氧化石墨烯（GO）和还原氧化石墨烯（rGO）处理的HepG 2细胞中使用OMICS，对石墨烯纳米材料的生物相互作用进行了全面的研究，特别是关于其差异表面功能化（氧化状态）。不同的表面化学（特别是氧化- O/C比）调节GO/rGO的疏水性/亲水性，这反过来又控制它们的生物相互作用潜力。类似的毒性反应GO和rGO均具有不同的剂量依赖性（细胞毒性、DNA损伤、氧化应激），但它们表现出不同的机制，例如，亲水性GO显示细胞摄取、NADPH氧化酶依赖的ROS形成、抗氧化/DNA修复/凋亡相关基因的高度失调，相反，发现疏水性rGO主要吸附在细胞表面而没有内化，基因表达和通路分析表明，TGF β 1介导的信号转导在GO诱导的生物学/毒理学效应中起主要作用，而rGO可能通过TLR 4-NFkB通路引起宿主-病原体（病毒）相互作用和天然免疫应答。简而言之，GO/rGO不同的生物和分子机制归因于它们不同的表面氧化状态。(C)2013爱思唯尔有限公司保留所有权利。
The raised considerable concerns about the possible environmental health and safety impacts of graphene nanomaterials and their derivatives originated from their potential widespread applications. We performed a comprehensive study about biological interaction of grapheme nanomaterials, specifically in regard to its differential surface functionalization (oxidation status), by using OMICS in graphene oxide (GO) and reduced graphene oxide (rGO) treated HepG2 cells. Differential surface chemistry (particularly, oxidation - O/C ratio) modulates hydrophobicity/philicity of GO/rGO which in turn governs their biological interaction potentiality. Similar toxic responses (cytotoxicity, DNA damage, oxidative stress) with differential dose dependency were observed for both GO and rGO but they exhibited distinct mechanism, such as, hydrophilic GO showed cellular uptake, NADPH oxidase dependent ROS formation, high deregulation of antioxidant/DNA repair/apoptosis related genes, conversely, hydrophobic rGO was found to mostly adsorbed at cell surface without internalization, ROS generation by physical interaction, poor gene regulation etc. Global gene expression and pathway analysis displayed that TGF beta 1 mediated signaling played the central role in GO induced biological/toxicological effect whereas rGO might elicited host-pathogen (viral) interaction and innate immune response through TLR4-NFkB pathway. In brief, the distinct biological and molecular mechanisms of GO/rGO were attributed to their differential surface oxidation status. (C) 2013 Elsevier Ltd. All rights reserved.